pH-Sensitive Carrier Membrane Disruption for Drug Delivery
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Solution Overview
Problem
Current pH-sensitive carriers exhibit sensitivity at too low a pH or have inadequate function, and modifying pH-sensitive materials can decrease the activity of physiologically active substances, raising safety concerns, especially when using novel synthetic materials or viral components.
Innovation Solution
A pH-sensitive carrier comprising deoxycholic acid or its derivatives in combination with amphipathic substances like phosphatidylcholine or polyoxyethylene sorbitan monofatty acid esters, forming micellar particles that develop a membrane disruptive function promoting effect at weakly acidic pH, enhancing delivery of physiologically active substances to the cytosol.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pH-sensitive materials are modified to enhance function, then delivery efficiency is improved, but activity of physiologically active substances decreases
Solution Approach 1:
The patent uses pH-sensitive liposomes as intermediary carriers that respond to pH changes in the endosomal compartment. The liposomes incorporate pH-sensitive elements (CHEMS, oleic acid, PHC) that trigger membrane disruption at acidic pH, mediating the release of physiologically active substances into the cytosol without direct chemical modification of the substances themselves, thus preserving their activity while achieving enhanced delivery efficiency
2Measurement precision
If sensitivity threshold of pH-sensitive carrier is lowered, then specificity to acidic environments is improved, but functionality at physiological pH is reduced
Solution Approach 1:
The patent adjusts the pH sensitivity threshold by modifying the composition and structure of pH-sensitive elements within the liposome. By controlling the ratio of pH-sensitive elements to neutral lipids and adjusting the pKa values of incorporated compounds, the carrier achieves optimal sensitivity to endosomal pH (approximately pH 5-6) while maintaining stability and functionality at physiological pH (7.4), enabling precise targeting without sacrificing operational capability
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The carrier effectively delivers physiologically active substances to the cytosol by increasing membrane leakage and fusion at acidic pH, improving the efficacy of drug delivery while maintaining safety and pH sensitivity, suitable for treating diseases like cancer and inflammation.
Implementation Method 1
a pH sensitive carrier which includes at least one pH sensitive compound and at least one amphipathic substance and is capable of developing a membrane disruptive function promoting effect in response to a weakly acidic environment
Implementation Method 2
capable of developing a membrane disruptive function promoting effect in response to a weakly acidic environment
Data Source
AI summary
A method for treating tumor or inflammation in a patient in need thereof by administering a pH sensitive drug which includes a pH sensitive carrier including at least one amphipathic substance, and a physiologically active substance supported in the pH sensitive carrier to induce the pH sensitive carrier to develop a membrane disruptive function and to deliver the physiologically active substance to the site. The pH sensitive carrier can include at least one of deoxycholic acid, cholic acid, ursodeoxycholic acid, chenodeoxycholic acid, hyodeoxycholic acid, C27 bile acid, glycodeoxycholic acid, glycyrrhizic acid, glycyrrhetinic acid and salts thereof, and the amphipathic substance can include at least one of a phosphatidylcholine having 10 to 12 carbon atoms, a polyoxyethylene sorbitan monofatty acid ester having 12 to 18 carbon atoms, a sorbitan fatty acid ester having 16 to 18 carbon atoms, glycerol monooleate, glycerol dilaurate, glycerol distearate, glycerol dioleate, polyoxyethylene castor oil and α-tocopherol.